1. Field
One or more embodiments of the present invention relate to a composition for preventing or treating erectile dysfunction including angiopoietin-4 protein as an active ingredient.
2. Description of the Related Art
Erectile dysfunction is a male sexual dysfunction characterized by inability to achieve or maintain an erection sufficient for satisfactory sexual activity. Causes of erection dysfunction are classified into psychogenic and organic causes. Psychogenic erectile dysfunction is caused by an overaction of the sympathetic nervous system due to psychological and emotional impact such as hypersecretion of noradrenaline, increase in tone of corpus cavernosum smooth muscle, and suppression of neurotransmitter secretion. Organic erectile dysfunction is classified into neurogenic erectile dysfunction, vasculogenic erectile dysfunction, and endocrine erectile dysfunction according to the cause thereof.
The vasculogenic erectile dysfunction is caused by damage to penile vascular endothelial cells due to hyperlipidemia, diabetes, hypertension, smoking, cardiovascular diseases, and the like. The vascular erectile dysfunction exhibits insufficient secretion of relaxation neurotransmitters such as nitric oxide (NO) in vascular endothelial cells.
Recently, more research on the organic causes has been conducted, and phosphodiesterase-5 (PDE-5) inhibitors for oral administration such as Viagra (sildenafil citrate) have been generally used to treat erectile dysfunction worldwide. Such medications for oral administration are effective for the treatment of erectile dysfunction via induction of erection by increasing blood flow to the corpus cavernosum. The blood flow is increased since the PDE-5 inhibitor that is specifically distributed in the corpus cavernosum increases a concentration of cGMP. However, side effects, such as headache, facial flushing, indigestion, and heart attack, have been reported, and PDE-5 inhibitor-based drugs such as Viagra cannot be fundamental treatment for erectile dysfunction since they temporarily control molecular level mechanism of expression of proteins and related factors thereof. Moreover, such medications are not highly effective for the treatment of diabetes-induced erectile dysfunction, and the therapeutic effect cannot last for a long period of time.
Thus, there is a need to develop a therapeutic agent for treating erectile dysfunction which fundamentally treating an abnormal vascular structure of the penis and has long-lasting effect.
Meanwhile, angiopoietin-4 protein that is a protein belonging to the angiopoietin family has a coiled-coil domain and a fibrinogen-like domain which are structurally similar to each other. Human angiopoietin-4 protein and mouse angiopoietin-3 are orthologs sharing 65% overall amino acid sequence identity (Valenzuela D M et al., Proc Natl Acad Sci U.S.A., 96(5), pp 1904-9, 1999). Similarly to other angiopoietins, it is known that angiopoietin-4 protein mainly binds to Tie-2 receptor tyrosine kinase, and there has been reported that angiopoietin-4 protein transmits a signal by phosphorylating a Tie-2 receptor in the same manner as angiopoietin-1 (Lee H J et al., FASEB J, 18(11), pp 1200-8, 2004). In addition, there has been reported that angiopoietin-4 protein induces angiogenesis in mouse cornea by activating the Tie-2 receptor (Lee H J et al., FASEB J, 18(11), pp 1200-8, 2004). However, effect of angiopoietin-4 protein on the prevention or treatment of erectile dysfunction has not been reported, and research thereon has not been carried out.
Accordingly, the present inventors conducted research on a composition for preventing or treating erectile dysfunction and discovered that angiopoietin-4 protein has an effect on the treatment for erectile dysfunction since angiopoietin-4 protein increases intracavernous pressure via induction of regeneration of penile vascular endothelial cells by increasing an endothelial cell-specific protein level.